Oral Presentation 8th Australasian Virology Society Meeting and 11th Annual Meeting of the Australian Centre for Hepatitis & HIV Virology Meeting 2015

Enrichment of HIV in cells that express CCR6 and CXCR3 in blood and rectal tissue in HIV-infected individuals on cART (#50)

Jenny L Anderson 1 2 3 , Remi Fromentin 4 5 , Ajantha Solomon 1 2 3 , Nicolas Chomont 4 5 , Elizabeth Sinclair 6 , Gabriela Khoury 2 3 , Paul U Cameron 1 2 3 7 , Lorrie Epling 6 , Rebecca Hoh 6 , Frederick M Hecht 6 , Steven G Deeks 6 , Sharon R Lewin 1 2 3 7
  1. Peter Doherty Institute for Infection and Immunity, The University of Melbourne, Melbourne, VIC, Australia
  2. Infectious Diseases, Monash University, Melbourne, VIC, Australia
  3. Centre for Biomedical Research, Burnet Institute, Melbourne, VIC, Australia
  4. Microbiology, Infectious Diseases and Immunology, The University of Montreal, Montreal, Quebec, Canada
  5. Vaccine and Gene Therapy Institute of Florida, Port St Lucie, FL, USA
  6. Medicine, University of California, San Francisco, CA, USA
  7. Infectious Diseases, The Alfred Hospital, Melbourne, VIC, Australia

Pretreating resting CD4+ T-cells with chemokines that bind chemokine receptors (CKR) CCR7, CCR6 (R6) or CXCR3 (X3) enable direct latent HIV infection in vitro. As these CKR are also critical for homing of CD4+ T-cells to tissue, we examined if the expression of CKR and their chemokine ligands was related to HIV reservoir size in blood, rectal and lymph node (LN) tissue in patients on cART.

Whole blood (n=48), leukapheresis (n=20), rectal biopsies (n=19) and inguinal LN biopsies (n=8) were collected from HIV+ individuals on cART ≥3 years. The HIV reservoir in sorted T-cells was measured using qPCR and RT-qPCR for HIV integrated DNA and unspliced RNA (US-RNA) respectively. CKR expression was measured via flow cytometry. Chemokine expression in plasma was measured via Luminex and in tissue via RT-qPCR for chemokine mRNA.

In blood, HIV integrated DNA was significantly enriched in R6+X3+ central memory CD4+ T-cells versus R6+X3-, R6-X3+ and R6-X3- subsets (p<0.001). Rectal CD4+ T-cells had significantly more integrated DNA (p=0.0001) and US-RNA (p=0.0079) than blood. Rectal tissue also harboured high proportions of R6+X3+ memory CD4+ T-cells than blood and LN (median 70%, 21% and 12% respectively). Preliminary statistical analyses indicate that in the rectum, integrated HIV DNA positively correlated with CXCR3 ligand mRNA (CXCL10 p=0.016, CXCL11 p=0.040). Rectal HIV integrated DNA (p=0.003) and US-RNA (p=0.014) positively correlated with rectal R6+X3- memory T-cell proportion. In the LN, the HIV reservoir did not correlate with R6 and/or X3 memory T-cell proportion nor chemokine mRNA expression.

In patients on cART, rectal tissue has a high frequency of infected cells and this may be associated with migration of cells that express either or both CCR6 or CXCR3. Interventions targeting CCR6 and/or CXCR3 may prove useful in curative strategies.